The product of both the viral and cellular myc genes has been implicated as being a primary mediator of events leading to cellular transformation. In addition, the product of the c-myc gene appears to play an important role in the regulation of certain steps in normal cell division and differentiation. The long range goals are to understand, at the molecular level, the function of the myc gene product in both normal and malignant cells. The specific aims of the experiments outlined in this proposal are first, to use site-directed mutagenesis techniques to generate mutations in the myc gene that specifically alter the biological consequences of the myc gene expression. Second, the alteration in phenotype induced by specific mutations will be assessed in several cells systems, including avian fibroblasts and hematopoietic cells, mouse hematopoietic cells and mouse 10T1/2 cells. Third, biochemical experiments will attempt to define the important structural domains required for DNA binding, nuclear and subnuclear localization, gene activation and sites of protein phosphorylation. Such experiments will permit us to define the important structural features of the myc protein and determine how these structural/functional domains govern the activity of the myc protein.